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Science : Do shattered spines need a cleanup?

28 September 1996

By Gary Eastwood

THE damaged nerves of people paralysed by spinal injuries might in future be
repaired by cells from their own immune systems.

Michal Schwartz and her colleagues at the Weizmann Institute of Science in
Rehovot, Israel, have found that immune cells called macrophages can repair
severed optic nerves in rats. They believe the same technique should also work
in humans who have suffered injuries to their central nervous system (CNS).

In mammals, nerve cells in the spinal cord, optic nerve and brain cannot
regenerate if they are severed. But in lower vertebrates, such as fish and
amphibians, such regeneration is possible. In these animals, macrophages zoom in
on damaged nerve cells, mopping up cellular debris and releasing chemicals that
promote tissue growth. The CNS of mammals, however, is an “immunoprivileged”
tissue—in other words macrophages and other immune cells are excluded.
Even if the cells are transplanted into a section of severed spinal cord, they
remain inactive.

Schwartz and her colleagues have been looking for a way to overcome this
suppression. In this month’s issue of The FASEB Journal (vol 10, p
1296), they say that the secret is to incubate macrophages with nerves from
outside the CNS—which are repaired by macrophages even in mammals.

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The researchers cultured macrophages alongside segments of sciatic nerve
cells taken from rats’ hips. This activated the macrophages, priming them to
engulf debris from injured cells and to release their chemical growth signals.
When the cells were transplanted into severed rat optic nerves, the damaged
neurons regrew.

Schwartz warns that the rat study is only the first step on the long road
towards clinical applications. The researchers had to kill their rats to
determine whether their nerves had regrown, so it is unclear whether the
repaired nerves were able to function normally.

The method also raises the possibility of damaging side effects. Schwartz
believes that macrophages are normally excluded from the mammalian CNS because
their urge to “tidy up” would disrupt the subtle neural wiring required for
learning, memory and other CNS functions.

The researchers are concerned that macrophages applied to a spinal injury
might travel along nerve fibres and disrupt other parts of the CNS. They want to
try to restrict this migration by carefully controlling the site where they
release the macrophages. “I am not claiming I have a cure today,” says Schwartz.
“We need to find the optimal balance between regeneration and degeneration.”

Fred Geisler, a surgeon at the Chicago Institute of Neurosurgery and
Neuroresearch, predicts that a whole range of techniques will be required if
doctors are ever to restore sensation and movement to people with spinal
injuries.

“Where this will fit into the clinical arena remains to be seen, but it
represents a novel approach,” says Geisler. “They have identified what could be
a very important component of therapy.”